The objective of this Phase II application is the commercial development of CEA-ImmunoPET for breast cancer imaging. CEA-ImmunoPET is a two-component product system comprising TF2, a trivalent, bispecific, anti-CEA x anti-HSG constructs made by the Dock and Lock (DNL) method, and 68Ga-IMP288, a DOTA- derivatized di-HSG peptide radiolabeled with 68Ga. In the Phase I SBIR (1 R43 CA123985-01), we have achieved significant advancement towards clinical development of TF2 for radioimmunodetection and therapy of CEA-positive tumors with IMP288 radiolabeled with 111In or 124I. We have established the feasibility of clinical development of the TF2/IMP288 pretargeting system by (a) further optimizing the process of producing TF2 from cell cultures; (b) completing preclinical studies that have characterized the pharmacokinetic behavior of TF2 and IMP288 as well as obtaining the conditions that will lead to optimal pretargeting of tumors, (c) evaluating the tissue binding properties of TF2 and to some degree IMP288, and (d) initiating important acute toxicity studies that have shown the safety of both TF2 and IMP288. In this Phase II application, we will complete the preclinical development of TF2 and 68Ga-IMP288 to qualify its use for clinical trials, establish optimal pretargeting conditions in mouse models bearing human tumor xenografts that differ in the expression levels of CEA, and to submit an IND to the FDA. We plan to be in position to begin clinical trials for breast cancer imaging at the end of the Phase II funding period. PUBLIC HEALTH RELEVANCE: Pretargeting with CEA-ImmunoPET has the potential to become a breast cancer imaging technique that is convenient, non-invasive, non-scarring, highly sensitive and yet capable of clearly differentiating between malignant and non-malignant tissues. [unreadable] [unreadable] [unreadable]